Microbiome and metabolome integrally reveal the anti-depression effects of Cistanche deserticola polysaccharides from the perspective of gut homeostasis.

Polysaccharides are one of the active components of Cistanche deserticola (CD). Cistanche deserticola polysaccharides (CDPs) significantly regulate gut microbiota, immune activity, and neuroprotective functions. However, it merely scratches the surface that the anti-depression effects of CDPs. We aimed to demonstrate the anti-depression effects of CDPs and the underlying mechanisms from the perspectives of gut homeostasis by behavioral evaluations and applying integrally microbiome, metabolome, and molecular biology. CDPs showed significant effects on improving abnormal behaviors of depressed rats. Additionally, CDPs maintained Th17/Treg balance and modulated gut immunity of depressed rats. Comprehensive microbiome and metabolome analysis showed that CDPs significantly ameliorated abundances of beneficial bacteria, and increased the contents of SCFAs, consequently maintaining gut homeostasis. Besides, the anti-depression effects of CDPs involved in amino acid metabolism including BCAAs, glutamine, etc., maintaining metabolic balance. The current findings provide not only deep understanding of depression focusing on gut, but also evidence about the anti-depression effects of CDPs, broadening clinic applications of CDPs. Of note, the present study is of significance in a long run, in terms of providing novel strategies and protocols for revealing mechanisms of anti-depression drugs, and for the discovery of new antidepressants and functional foods from natural products.